tbuckley/cabot-search huggingface dataset:
An Antibacterial and Anti‐Oxidative Hydrogel Dressing for Promoting Diabetic Wound Healing and Real‐Time Monitoring Wound pH Conditions with a NIR Fluorescent Imaging System
Authors: Yuange Zong, Beige Zong, Ruyan Zha, Yi Zhang, Xianghong Li, Yanying Wang, Huaifang Fang, Wing‐Leung Wong, Chunya Li
Journal: Advanced Healthcare Materials (2023)

The design and synthesis of multifunctional chitosan hydrogels based on polymerized ionic liquid and a near-infrared (NIR) fluorescent probe (PIL-CS) is a promising strategy, which not only prevents the transition from acute to chronic wounds, but also provides prompt measures regarding microenvironmental alterations in chronic wounds. PIL-CS hydrogel can real-time visualize wound pH through in vivo NIR fluorescent imaging and also feature the pH-responsive sustained drug release, such as antioxidant, to eliminate reactive oxygen species (ROS) and to boost diabetic wound healing. PIL-CS hydrogel is specific, sensitive, stable, and reversible in response to pH changes at the wound site. It, therefore, enables real-time monitoring for a dynamic pH change in the microenvironment of irregular wounds. PIL-CS hydrogel is also designed to possess many merits including high water containment and swelling rate, good biocompatibility, electrical conductivity, antifreeze, tissue adhesion, hemostatic performance, and efficient antibacterial activity against MRSA. In vivo studies showed that PIL-CS hydrogel provided fast diabetic wound healing support, promoted vascular endothelial growth factor (VEGF) production, and reduced ROS and tumor necrosis factor (TNF-α) generation. The results support that the hydrogels coupled with NIR fluorescent probes can be an excellent diabetic wound dressing for enhancing and real-time monitoring skin restoration and regeneration.
Machine learning links unresolving secondary pneumonia to mortality in patients with severe pneumonia, including COVID-19
Authors: Catherine A. Gao, Nikolay S. Markov, Thomas Stoeger, Anna Pawlowski, Mengjia Kang, Prasanth Nannapaneni, Rogan A. Grant, Chiagozie Pickens, James M. Walter, Jacqueline M. Kruser, Luke Rasmussen, Daniel Schneider, Justin Starren, Helen K. Donnelly, Alvaro Donayre, Yuan Luo, G.R. Scott Budinger, Richard G. Wunderink, Alexander V. Misharin, Benjamin D. Singer
Journal: Journal of Clinical Investigation (2023)

BACKGROUNDDespite guidelines promoting the prevention and aggressive treatment of ventilator-associated pneumonia (VAP), the importance of VAP as a driver of outcomes in mechanically ventilated patients, including patients with severe COVID-19, remains unclear. We aimed to determine the contribution of unsuccessful treatment of VAP to mortality for patients with severe pneumonia.METHODSWe performed a single-center, prospective cohort study of 585 mechanically ventilated patients with severe pneumonia and respiratory failure, 190 of whom had COVID-19, who underwent at least 1 bronchoalveolar lavage. A panel of intensive care unit (ICU) physicians adjudicated the pneumonia episodes and endpoints on the basis of clinical and microbiological data. Given the relatively long ICU length of stay (LOS) among patients with COVID-19, we developed a machine-learning approach called CarpeDiem, which grouped similar ICU patient-days into clinical states based on electronic health record data.RESULTSCarpeDiem revealed that the long ICU LOS among patients with COVID-19 was attributable to long stays in clinical states characterized primarily by respiratory failure. While VAP was not associated with mortality overall, the mortality rate was higher for patients with 1 episode of unsuccessfully treated VAP compared with those with successfully treated VAP (76.4% versus 17.6%, P < 0.001). For all patients, including those with COVID-19, CarpeDiem demonstrated that unresolving VAP was associated with a transitions to clinical states associated with higher mortality.CONCLUSIONSUnsuccessful treatment of VAP is associated with higher mortality. The relatively long LOS for patients with COVID-19 was primarily due to prolonged respiratory failure, placing them at higher risk of VAP.FUNDINGNational Institute of Allergy and Infectious Diseases (NIAID), NIH grant U19AI135964; National Heart, Lung, and Blood Institute (NHLBI), NIH grants R01HL147575, R01HL149883, R01HL153122, R01HL153312, R01HL154686, R01HL158139, P01HL071643, and P01HL154998; National Heart, Lung, and Blood Institute (NHLBI), NIH training grants T32HL076139 and F32HL162377; National Institute on Aging (NIA), NIH grants K99AG068544, R21AG075423, and P01AG049665; National Library of Medicine (NLM), NIH grant R01LM013337; National Center for Advancing Translational Sciences (NCATS), NIH grant U01TR003528; Veterans Affairs grant I01CX001777; Chicago Biomedical Consortium grant; Northwestern University Dixon Translational Science Award; Simpson Querrey Lung Institute for Translational Science (SQLIFTS); Canning Thoracic Institute of Northwestern Medicine.
Assessment of Gender-Specific COVID-19 Case Fatality Risk per Malignant Neoplasm Type
Authors: Koji Matsuo, Rachel S. Mandelbaum, Andrew Vallejo, Maximilian Klar, Lynda D. Roman, Jason D. Wright
Journal: JAMA Oncology (2023)

While the characteristics of COVID-19 infection and mortality among patients with a malignant neoplasm have previously been examined, little data are available for gender-specific COVID-19 mortality.
Gene therapy ameliorates spontaneous seizures associated with cortical neuron loss in a Cln2R207X mouse model
Authors: Keigo Takahashi, Elizabeth M. Eultgen, Sophie H. Wang, Nicholas R. Rensing, Hemanth R. Nelvagal, Joshua T. Dearborn, Olivier Danos, Nicholas Buss, Mark S. Sands, Michael Wong, Jonathan D. Cooper
Journal: Journal of Clinical Investigation (2023)

Although a disease-modifying therapy for classic late infantile neuronal ceroid lipofuscinosis (CLN2 disease) exists, poor understanding of cellular pathophysiology has hampered the development of more effective and persistent therapies. Here, we investigated the nature and progression of neurological and underlying neuropathological changes in Cln2R207X mice, which carry one of the most common pathogenic mutations in human patients but are yet to be fully characterized. Long-term electroencephalography recordings revealed progressive epileptiform abnormalities, including spontaneous seizures, providing a robust, quantifiable, and clinically relevant phenotype. These seizures were accompanied by the loss of multiple cortical neuron populations, including those stained for interneuron markers. Further histological analysis revealed early localized microglial activation months before neuron loss started in the thalamocortical system and spinal cord, which was accompanied by astrogliosis. This pathology was more pronounced and occurred in the cortex before the thalamus or spinal cord and differed markedly from the staging seen in mouse models of other forms of neuronal ceroid lipofuscinosis. Neonatal administration of adeno-associated virus serotype 9-mediated gene therapy ameliorated the seizure and gait phenotypes and prolonged the life span of Cln2R207X mice, attenuating most pathological changes. Our findings highlight the importance of clinically relevant outcome measures for judging preclinical efficacy of therapeutic interventions for CLN2 disease.
Lack of seroprotection against diphtheria in the Austrian population, in light of reported diphtheria cases in Europe, 2022
Authors: Angelika Wagner, Joanna Jasinska, Daniela Schmid, Michael Kundi, Ursula Wiedermann
Journal: Eurosurveillance (2023)

Following an increase in diphtheria cases in Europe since 2022, we retrospectively estimated the prevalence of seroprotection against diphtheria and tetanus in 10,247 Austrian residents (population: 8,978,929) voluntarily tested between 2018 and 2022. Lack of seroprotection against diphtheria was found in 36% compared with 4% against tetanus. The geometric mean antibody concentration against tetanus was 7.9-fold higher compared with that for diphtheria. Raising awareness of regular booster vaccinations against diphtheria in combination with tetanus and pertussis is urgently needed.
Assessment of a Genomic Assay in Patients With <i>ERBB2</i>-Positive Breast Cancer Following Neoadjuvant Trastuzumab-Based Chemotherapy With or Without Pertuzumab
Authors: Coralia Bueno-Muiño, Isabel Echavarría, Sara López-Tarruella, Marta Roche-Molina, María del Monte-Millán, Tatiana Massarrah, Yolanda Jerez, Francisco Ayala de la Peña, José Ángel García-Sáenz, Fernando Moreno, Álvaro Rodríguez-Lescure, Diego Malón-Giménez, Ana Isabel Ballesteros García, Mercedes Marín-Aguilera, Patricia Galván, Fara Brasó-Maristany, Adrienne G. Waks, Sara M. Tolaney, Elizabeth A. Mittendorf, Ana Vivancos, Patricia Villagrasa, Joel. S. Parker, Charles M. Perou, Laia Paré, Guillermo Villacampa, Aleix Prat, Miguel Martín
Journal: JAMA Oncology (2023)

Biomarkers to guide the use of pertuzumab in the treatment of early-stage ERBB2 (formerly HER2)-positive breast cancer beyond simple ERBB2 status are needed.
<i>N6</i>-Methyladenosine Promotes Translation of VEGFA to Accelerate Angiogenesis in Lung Cancer
Authors: Haisheng Zhang, Jiawang Zhou, Jiexin Li, Zhaotong Wang, Zhuojia Chen, Ziyan Lv, Lichen Ge, Guoyou Xie, Guoming Deng, Yalan Rui, Hongbing Huang, Likun Chen, Hongsheng Wang
Journal: Cancer Research (2023)

Abstract Angiogenesis is hijacked by cancer to support tumor growth. RNA modifications such as N6-methyladenosine (m6A) can regulate several aspects of cancer, including angiogenesis. Here, we find that m6A triggers angiogenesis in lung cancer by upregulating VEGFA, a central regulator of neovasculature and blood vessel growth. m6A-sequencing and functional studies confirmed that m6A modification of the 5′UTR (untranslated region) of VEGFA positively regulates its translation. Specifically, methylation of a 5′UTR internal ribosome entry site (IRES) recruited the YTHDC2/eIF4GI complex to trigger cap-independent translation initiation. Intriguingly, the m6A methylation site A856 of the 5′UTR was located within the conserved upstream open reading frame (uORF) of VEGFA IRES-A, which overcomes uORF-mediated translation suppression while facilitating G-quadruplex–induced translation of VEGFA. Targeted specific demethylation of VEGFA m6A significantly decreased expression of VEGFA and reduced lung cancer cell–driven angiogenesis. In vivo and clinical data confirmed the positive effects of m6A modification of VEGFA on angiogenesis and tumor growth of lung cancer. This study not only reveals that the m6A/VEGFA axis is a potential target for lung cancer therapy but also expands our understanding of the impact of m6A modification of IRES in the 5′UTR of mRNA on translation regulation. Significance: Methylation of the 5′UTR IRES of VEGFA mRNA increases cap-independent translation via recruitment of the YTHDC2/eIF4GI complex, which stimulates angiogenesis to promote lung tumor growth.
Effectiveness and Safety of Dapagliflozin for Black and White Patients With Chronic Kidney Disease in North and South America
Authors: Priya Vart, Niels Jongs, David C. Wheeler, Hiddo J. L. Heerspink, Anna Maria Langkilde, Glenn M. Chertow
Journal: JAMA Network Open (2023)

This secondary analysis of a randomized clinical trial investigates the relative effectiveness and safety of the sodium-glucose cotransporter-2 inhibitor dapagliflozin for Black and White patients with chronic kidney disease (CKD) in North and South America.
Longitudinal Analysis of Change in Mammographic Density in Each Breast and Its Association With Breast Cancer Risk
Authors: Shu Jiang, Debbie L. Bennett, Bernard A. Rosner, Graham A. Colditz
Journal: JAMA Oncology (2023)

Although breast density is an established risk factor for breast cancer, longitudinal changes in breast density have not been extensively studied to determine whether this factor is associated with breast cancer risk.
Effectiveness of Monovalent mRNA COVID-19 Vaccination in Preventing COVID-19–Associated Invasive Mechanical Ventilation and Death Among Immunocompetent Adults During the Omicron Variant Period — IVY Network, 19 U.S. States, February 1, 2022–January 31, 2023
Authors: Jennifer DeCuir, Diya Surie, Yuwei Zhu, Manjusha Gaglani, Adit A. Ginde, David J. Douin, H. Keipp Talbot, Jonathan D. Casey, Nicholas M. Mohr, Tresa McNeal, Shekhar Ghamande, Kevin W. Gibbs, D. Clark Files, David N. Hager, Minh Phan, Matthew E. Prekker, Michelle N. Gong, Amira Mohamed, Nicholas J. Johnson, Jay S. Steingrub, Ithan D. Peltan, Samuel M. Brown, Emily T. Martin, Arnold S. Monto, Akram Khan, William S. Bender, Abhijit Duggal, Jennifer G. Wilson, Nida Qadir, Steven Y. Chang, Christopher Mallow, Jennie H. Kwon, Matthew C. Exline, Adam S. Lauring, Nathan I. Shapiro, Cristie Columbus, Robert Gottlieb, Ivana A. Vaughn, Mayur Ramesh, Lois E. Lamerato, Basmah Safdar, Natasha Halasa, James D. Chappell, Carlos G. Grijalva, Adrienne Baughman, Kelsey N. Womack, Jillian P. Rhoads, Kimberly W. Hart, Sydney A. Swan, Nathaniel Lewis, Meredith L. McMorrow, Wesley H. Self
Journal: MMWR Morbidity and Mortality Weekly Report (2023)

As of April 2023, the COVID-19 pandemic has resulted in 1.1 million deaths in the United States, with approximately 75% of deaths occurring among adults aged ≥65 years (1). Data on the durability of protection provided by monovalent mRNA COVID-19 vaccination against critical outcomes of COVID-19 are limited beyond the Omicron BA.1 lineage period (December 26, 2021-March 26, 2022). In this case-control analysis, the effectiveness of 2-4 monovalent mRNA COVID-19 vaccine doses was evaluated against COVID-19-associated invasive mechanical ventilation (IMV) and in-hospital death among immunocompetent adults aged ≥18 years during February 1, 2022-January 31, 2023. Vaccine effectiveness (VE) against IMV and in-hospital death was 62% among adults aged ≥18 years and 69% among those aged ≥65 years. When stratified by time since last dose, VE was 76% at 7-179 days, 54% at 180-364 days, and 56% at ≥365 days. Monovalent mRNA COVID-19 vaccination provided substantial, durable protection against IMV and in-hospital death among adults during the Omicron variant period. All adults should remain up to date with recommended COVID-19 vaccination to prevent critical COVID-19-associated outcomes.
Postoperative risk of IDH mutant glioma–associated seizures and their potential management with IDH mutant inhibitors
Authors: Michael R. Drumm, Wenxia Wang, Thomas K. Sears, Kirsten Bell-Burdett, Rodrigo Javier, Kristen Y. Cotton, Brynna Webb, Kayla Byrne, Dusten Unruh, Vineeth Thirunavu, Jordain Walshon, Alicia Steffens, Kathleen McCortney, Rimas V. Lukas, Joanna J. Phillips, Esraa Mohamed, John D. Finan, Lucas Santana-Santos, Amy B. Heimberger, Colin K. Franz, Jonathan Kurz, Jessica W. Templer, Geoffrey T. Swanson, Craig Horbinski
Journal: Journal of Clinical Investigation (2023)

Seizures are a frequent complication of adult-type diffuse gliomas, and are often difficult to control with medications. Gliomas with mutations in isocitrate dehydrogenase 1 or 2 (IDHmut) are more likely than IDH–wild type (IDHwt) gliomas to cause seizures as part of their initial clinical presentation. However, whether IDHmut is also associated with seizures during the remaining disease course, and whether IDHmut inhibitors can reduce seizure risk, are unclear. Clinical multivariable analyses showed that preoperative seizures, glioma location, extent of resection, and glioma molecular subtype (including IDHmut status) all contributed to postoperative seizure risk in adult-type diffuse glioma patients, and that postoperative seizures were often associated with tumor recurrence. Experimentally, the metabolic product of IDHmut, d-2-hydroxyglutarate, rapidly synchronized neuronal spike firing in a seizure-like manner, but only when non-neoplastic glial cells were present. In vitro and in vivo models recapitulated IDHmut glioma–associated seizures, and IDHmut inhibitors currently being evaluated in glioma clinical trials inhibited seizures in those models, independent of their effects on glioma growth. These data show that postoperative seizure risk in adult-type diffuse gliomas varies in large part by molecular subtype, and that IDHmut inhibitors could play a key role in mitigating such risk in IDHmut glioma patients.
Mpox outbreak among men who have sex with men in Amsterdam and Rotterdam, the Netherlands: no evidence for undetected transmission prior to May 2022, a retrospective study
Authors: Henry J de Vries, Hannelore M Götz, Sylvia Bruisten, Annemiek A van der Eijk, Maria Prins, Bas B Oude Munnink, Matthijs RA Welkers, Marcel Jonges, Richard Molenkamp, Brenda M Westerhuis, Leonard Schuele, Arjen Stam, Marjan Boter, Elske Hoornenborg, Daphne Mulders, Mariken van den Lubben, Marion Koopmans
Journal: Eurosurveillance (2023)

Since May 2022, over 21,000 mpox cases have been reported from 29 EU/EEA countries, predominantly among men who have sex with men (MSM). The Netherlands was the fourth most affected country in Europe, with more than 1,200 cases and a crude notification rate of 70.7 per million population. The first national case was reported on 10 May, yet potential prior transmission remains unknown. Insight into prolonged undetected transmission can help to understand the current outbreak dynamics and aid future public health interventions. We performed a retrospective study and phylogenetic analysis to elucidate whether undetected transmission of human mpox virus (hMPXV) occurred before the first reported cases in Amsterdam and Rotterdam. In 401 anorectal and ulcer samples from visitors to centres for sexual health in Amsterdam or Rotterdam dating back to 14 February 2022, we identified two new cases, the earliest from 6 May. This coincides with the first cases reported in the United Kingdom, Spain and Portugal. We found no evidence of widespread hMPXV transmission in Dutch sexual networks of MSM before May 2022. Likely, the mpox outbreak expanded across Europe within a short period in the spring of 2022 through an international highly intertwined network of sexually active MSM.
Effect of listening to breathing recordings on self-reported breathlessness: a public experiment
Authors: Natasha Lovell, Simon N. Etkind, Joanna M. Davies, Wendy Prentice, Irene J. Higginson, Katherine E. Sleeman
Journal: European Respiratory Journal (2023)

<h3>Tweetable abstract</h3> <b>This public experiment – a collaboration between the Cicely Saunders Institute and Science Gallery London – found that listening to audio recordings of breathlessness resulted in a noticeable increase in self-reported breathlessness.</b>https://bit.ly/3o8py2Q
Nicotine promotes e-cigarette vapour-induced lung inflammation and structural alterations
Authors: Elsa T. Roxlau, Oleg Pak, Stefan Hadzic, Claudia F. Garcia-Castro, Marija Gredic, Cheng-Yu Wu, Julia Schäffer, Balachandar Selvakumar, Alexandra Pichl, David Spiegelberg, Janik Deutscher, Mariola Bednorz, Katharina Schäfer, Simone Kraut, Djuro Kosanovic, Esraa M. Zeidan, Baktybek Kojonazarov, Susanne Herold, Ievgen Strielkov, Andreas Guenther, Jochen Wilhelm, Mohamed M.A. Khalifa, Ashraf Taye, Ralf P. Brandes, Matthias Hecker, Friedrich Grimminger, Hossein A. Ghofrani, Ralph T. Schermuly, Werner Seeger, Natascha Sommer, Norbert Weissmann
Journal: European Respiratory Journal (2023)

Background Electronic cigarette (e-cigarette) vapour is gaining popularity as an alternative to tobacco smoking and can induce acute lung injury. However, the specific role of nicotine in e-cigarette vapour and its long-term effects on the airways, lung parenchyma and vasculature remain unclear. Results In vitro exposure to nicotine-containing e-cigarette vapour extract (ECVE) or to nicotine-free e-cigarette vapour extract (NF ECVE) induced changes in gene expression of epithelial cells and pulmonary arterial smooth muscle cells (PASMCs), but ECVE in particular caused functional alterations ( e.g. a decrease in human and mouse PASMC proliferation by 29.3±5.3% and 44.3±8.4%, respectively). Additionally, acute inhalation of nicotine-containing e-cigarette vapour (ECV) but not nicotine-free e-cigarette vapour (NF ECV) increased pulmonary endothelial permeability in isolated lungs. Long-term in vivo exposure of mice to ECV for 8 months significantly increased the number of inflammatory cells, in particular lymphocytes, compared to control and NF ECV in the bronchoalveolar fluid (BALF) (ECV: 853.4±150.8 cells·mL −1 ; control: 37.0±21.1 cells·mL −1 ; NF ECV: 198.6±94.9 cells·mL −1 ) and in lung tissue (ECV: 25.7±3.3 cells·mm −3 ; control: 4.8±1.1 cells·mm −3 ; NF ECV: 14.1±2.2 cells·mm −3 ). BALF cytokines were predominantly increased by ECV. Moreover, ECV caused significant changes in lung structure and function ( e.g. increase in airspace by 17.5±1.4% compared to control), similar to mild tobacco smoke-induced alterations, which also could be detected in the NF ECV group, albeit to a lesser degree. In contrast, the pulmonary vasculature was not significantly affected by ECV or NF ECV. Conclusions NF ECV components induce cell type-specific effects and mild pulmonary alterations, while inclusion of nicotine induces significant endothelial damage, inflammation and parenchymal alterations.
Human memory B cells show plasticity and adopt multiple fates upon recall response to SARS-CoV-2
Authors: Yves Zurbuchen, Jan Michler, Patrick Taeschler, Sarah Adamo, Carlo Cervia, Miro E. Raeber, Ilhan E. Acar, Jakob Nilsson, Klaus Warnatz, Michael B. Soyka, Andreas E. Moor, Onur Boyman
Journal: Nature Immunology (2023)

Abstract The B cell response to different pathogens uses tailored effector mechanisms and results in functionally specialized memory B (B m ) cell subsets, including CD21 + resting, CD21 – CD27 + activated and CD21 – CD27 – B m cells. The interrelatedness between these B m cell subsets remains unknown. Here we showed that single severe acute respiratory syndrome coronavirus 2-specific B m cell clones showed plasticity upon antigen rechallenge in previously exposed individuals. CD21 – B m cells were the predominant subsets during acute infection and early after severe acute respiratory syndrome coronavirus 2-specific immunization. At months 6 and 12 post-infection, CD21 + resting B m cells were the major B m cell subset in the circulation and were also detected in peripheral lymphoid organs, where they carried tissue residency markers. Tracking of individual B cell clones by B cell receptor sequencing revealed that previously fated B m cell clones could redifferentiate upon antigen rechallenge into other B m cell subsets, including CD21 – CD27 – B m cells, demonstrating that single B m cell clones can adopt functionally different trajectories.
Sensory perception relies on fitness-maximizing codes
Authors: Jonathan Schaffner, Sherry Dongqi Bao, Philippe N. Tobler, Todd A. Hare, Rafael Polania
Journal: Nature Human Behaviour (2023)

Abstract Sensory information encoded by humans and other organisms is generally presumed to be as accurate as their biological limitations allow. However, perhaps counterintuitively, accurate sensory representations may not necessarily maximize the organism’s chances of survival. To test this hypothesis, we developed a unified normative framework for fitness-maximizing encoding by combining theoretical insights from neuroscience, computer science, and economics. Behavioural experiments in humans revealed that sensory encoding strategies are flexibly adapted to promote fitness maximization, a result confirmed by deep neural networks with information capacity constraints trained to solve the same task as humans. Moreover, human functional MRI data revealed that novel behavioural goals that rely on object perception induce efficient stimulus representations in early sensory structures. These results suggest that fitness-maximizing rules imposed by the environment are applied at early stages of sensory processing in humans and machines.